1,2,3-Triols, cyclic

Duan and Smith developed a diastereoselective electrophilic cyclization of carbonates derived from homoallylic alcohols 98 via reaction with iodine monobromide to afford a-iodocarbonates 99 (Figure 25.13). These can further be utilized as intermediates for the synthesis of epoxy alcohols, iodohydrins, diols, triols, cyclic carbonates, and so on ... 

Preferential formation of a 5-membered cyclic acetal is not a general rule in the steroid series e.g., the 1,3-dioxolane (23) is obtained directly from the parent triol (22) and acetone. 17,21-Acetals are obtained only by acetal exchange. ... 

The next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

It is clear then that more than one mechanism is operative for glycol fission. In the case of c -cyclopentanediols and camphanediols a cyclic ester is a necessary intermediate. For tra/js-decalin-9,10-diol a non-cyclic mechanism must operate which cannot function for cholestane-3/ ,6j8,7a-triol and is inefficient for /rans-camphanediols. It is pertinent that while the fission of glycols capable of forming cyclic esters proceeds several hundred times faster in benzene than in acetic acid, the reactions of trans-decalin-9,10-diol and tra/ij-hydrindane-l,6-diol are 4-5-fold slower in benzene . ... 

RhH(PPh3)4 (1 mol%) exhibited higher catalytic activity and promoted a complete reversal in stereoselectivity to provide the trans isomer of 24 and 25 as the major reaction product. The czs-cyclopentane 29, derived from optically active 28, was converted to the differentially protected cyclopentane triol 29, which, in turn, converted to the differentially protected tetrad 30, a key intermediate in the synthesis of enantiopure bioactive carbo-cyclic nucleosides [19]. 

A cyclic carbonate was utilized as a protecting group for the cw-diol system in butane-1,2,4-triol ... 

Vitexilactone, obtained from Vi tex cannabifolia (Verbenaceae), has been shown to have the structure (16). It has been correlated with rotundifuran. An interesting iron(ii)-catalysed decomposition of unsaturated cyclic peroxides derived from butadienes leads to 3-alkylfurans. This procedure has been used to convert the peroxide (17) from ds-biformene into the furan (18). Some diterpenoid furans are amongst the constituents of Austroeupatorium inulaefolium (Compositae). These include the diketone austrofolin (19), the corresponding 12-alcohol, and the 15-alcohol (20). A triol, austroinulin (21), was also identified. 

Polyoxypropylene triol-based urethane networks are simulated. Simulations show that cyclic molecules are present in substantial amounts in the sol fraction when the vhnmotr-. tin rss1.0. Simulations also show that the fractions of loops are much higher than those obtained from modified cascade theory. 01 lc r... 

Diols and polyols can participate in equilibria with boric acid in aqueous solution. The stability of polyolborates is determined by the number of OH groups in cis positions. Complexes with polyols are more stable than with diols, and 1,2-diol complexes are more stable than their 1,3-diol counterparts (Table 10) since the resulting five-membered chelate ring is unstrained.75120 In the case of 1,3,5-triols stable cage-like structures (5) and (6) are favored. Open-chain or five-membered cyclic polyols form more stable chelate complexes than their six-membered counterparts.120 Thus, chelates from alditols and ketohexoses are more stable than the corresponding aldose chelates (Table 10). Many polyols allow quantitative titrimetric determination of boric acid. Of these, mannitol remains the most widely used reagent on the basis of availability, cost and ease of handling.75... 

Cyc/ic iodocarbonates (10,210-211). Cyclic iodocarbonates are useful precursors to epoxy alcohols, obtained by hydrolysis with Amberlyst A26, OH7form, and to triols, formed on treatment with Amberlyst A26 in the C03 2 form.8 Example ... 

The situation is similar with cyclic boronates, which are prepared by the following procedure. Steroid (10 pmol) and the respective substituted boric acid (10 jumol) are dissolved in ethyl acetate (1 ml) and the mixture is allowed to stand for 5 min at room temperature. Under these conditions, 17,20-diols, 20,21-diols and 17,20,21-triols are converted completely into boronates. Cyclic boronate was mainly produced from 17,21-dihydroxy-20-ketone, but side-products also appeared, the formation of which could be suppressed by adding a 10% excess of the reagent [387—389]. Different substituents on the boron atom, such as methyl, n-butyl, tert.-butyl, cyclohexyl and phenyl, are interesting from the viewpoint of GC—MS application. They are further suitable for converting isolated hydroxyl groups into TMS or acetyl derivatives. 

Osmylation of diastereomerically pure P-hydroxy sulfoximines, derived from 2a and cyclic enones, with a catalytic amount of osmium tetroxide (5 mol%) and trimethylamine V-oxide (1.5 equiv) gives diastereomerically pure triols which on thermolysis yield 2,3-dihydroxy cyclic ketones in high enantiomeric purity ( 100% ee). Osmylation occurs syn to the sulfoximine group.74... 

As shown in Scheme 49, cyclic silyl ethers bearing the ethoxycarbonyl group anti to the 7-substituents 151 upon treatment with silica gel gave acyclic ethyl 7-hydroxy-a-[2-(hydroxydimethylsilyl)]carboxylates 287, and the subsequent reduction with diisobutylaluminium (DIBAL) followed by Tamao oxidation <1990OS96> gave the corresponding acyclic triols 288 <2004TL4329>. 

The 2-naphthylmethyl ether group250 288 was used to protect a single primary hydroxy group in syntheses of tetra-. penta- and hexa-saccharide chains from respiratory mucins.289 The requisite building block 155.2 [Scheme 4.155] was prepared by O-alkylation of the cyclic stannoxane prepared from triol 155.1 using 2-naphthylmethyl bromide Deprotection was efficiently achieved under mild conditions using DDQ as exemplified by the conversion of 1553 to 155A. 

In the synthesis of verrucarin J (55) by Fraser-Reid and coworkers [62], triol 109 was treated with pyridiniura dichromate (PDC) for 3 days, resulting in oxidative cleavage of the adjacent diol to the corresponding aldehyde and further oxidation of the presumed cyclic hemiacetal intermediate gave 55 in 50% yield (Scheme 37). 

By analogy to the halolactonization reaction, the synthesis of cyclic iodocarbonates has been studied with the aim of functionalizing a double bond under regio- and stereocontrol, starting from allylic or homoallylic alcohols. These heterocyclic intermediates are employed for the synthesis of epoxy alcohols, diols and triols. 

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